The proposed project will investigate the neuropharmacology of chlorinated alicyclic compounds, agents which enhance transmitter release at cholinergic synapses. The project will use a model in vitro system of the presynaptic nerve terminal, the synaptosome, which behaves much like an intact nerve with respect to transmitter release elicited by agents known to enhance acetylcholine release. The drugs proposed for study are chlorinated alicyclics, which are simple molecules of small molecular weight and which are ideally suited for an investigation of structure-activity relationships. The mosquitofish (Gambusia affinis) was selected as the experimental animal because much toxocological information on chlorinated alicyclics is already available for this species. Synaptosomes from brains of mosquitofish will be used to investigate the mechanism of neurotoxic action of the chlorinated alicyclics by studying: a) acetylcholine and glutamate release from synaptosomes under the influence of these drugs; and b) effects of these drugs on energy-dependent and -independent calcium fluxes in synaptosomes as the specific physiological parameter affected by these drugs. Electrophysiological studies will be conducted on the effects of these compounds on known cholinergic and glutaminergic synapses. These results, along with synaptosomal binding of the drugs and acute toxicity information, will be correlated to elucidate structure-activity relationships.